Morphological evidence of endomorphin as an agonist for the mu-opioid receptor in the rat spinal cord

2003 ◽  
Vol 341 (2) ◽  
pp. 107-110 ◽  
Author(s):  
Qing-Ping Wang ◽  
James E. Zadina ◽  
Jian-Lian Guan ◽  
Seiji Shioda
Keyword(s):  
Spinal Cord ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Morphological Evidence ◽  
Rat Spinal Cord ◽  
Mu Opioid

Antinociception by Spinal and Systemic Oxycodone: Why Does the Route Make a Difference?

2006 ◽  
Vol 105 (4) ◽  
pp. 801-812 ◽  
Author(s):  
Kim K. Lemberg ◽  
Vesa K. Kontinen ◽  
Antti O. Siiskonen ◽  
Kaarin M. Viljakka ◽  
Jari T. Yli-Kauhaluoma ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Opioid Receptor ◽  
Subcutaneous Administration ◽  
Receptor Activation ◽  
Mu Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Tail Flick ◽  
Hot Plate ◽  
Mu Opioid ◽  
Pressure Tests

Background The pharmacology of oxycodone is poorly understood despite its growing clinical use. The discrepancy between its good clinical effectiveness after systemic administration and the loss of potency after spinal administration led the authors to study the pharmacodynamic effects of oxycodone and its metabolites using in vivo and in vitro models in rats. Methods Male Sprague-Dawley rats were used in hot-plate, tail-flick, and paw-pressure tests to study the antinociceptive properties of morphine, oxycodone, and its metabolites oxymorphone and noroxycodone. Mu-opioid receptor agonist-stimulated GTPgamma[S] autoradiography was used to study G-protein activation induced by morphine, oxycodone, and oxymorphone in the rat brain and spinal cord. Spontaneous locomotor activity was measured to assess possible sedation or motor dysfunction. Naloxone and the selective kappa-opioid receptor antagonist nor-binaltorphimine were used to study the opioid receptor selectivity of the drugs. Results Oxycodone showed lower efficacy and potency to stimulate GTPgamma[S] binding in the spinal cord and periaqueductal gray compared with morphine and oxymorphone. This could relate to the fact that oxycodone produced only weak naloxone-reversible antinociception after intrathecal administration. It also suggests that the metabolites may have a role in oxycodone-induced analgesia in rats. Intrathecal oxymorphone produced strong long-lasting antinociception, whereas noroxycodone produced antinociception with very high doses only. Subcutaneous administration of oxycodone and oxymorphone produced thermal and mechanical antinociception that was reversed by naloxone but not by nor-binaltorphimine. Oxymorphone was more potent than oxycodone, particularly in the hot-plate and paw-pressure tests. Conclusions The low intrathecal potency of oxycodone in rats seems be related to its low efficacy and potency to stimulate mu-opioid receptor activation in the spinal cord.

Effects of Remifentanil on N -methyl-d-aspartate Receptor

2005 ◽  
Vol 102 (6) ◽  
pp. 1235-1241 ◽  
Author(s):  
Emmanuel Guntz ◽  
Hélène Dumont ◽  
Céline Roussel ◽  
David Gall ◽  
François Dufrasne ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Opioid Receptor ◽  
Receptor Activation ◽  
Mu Opioid Receptor ◽  
Induced Current ◽  
Mu Opioid ◽  
Inward Current ◽  
Nmda Current ◽  
Nmda Receptor Activation

Background Remifentanil hydrochloride contained in Ultiva (GlaxoSmithKline, Genval, Belgium) has been incriminated in difficult postoperative pain management, promotion of hyperalgesia, and direct N-methyl-D-aspartate (NMDA) receptor activation, but the involved mechanisms have remained unclear. In the current study, the authors investigated the effects of remifentanil hydrochloride, with and without its vehicle, glycine, on the activation of NMDA receptors and the modulation of NMDA-induced current on neurons inside the lamina II from the dorsal horn of rat spinal cord. Methods To test these effects, whole cell patch clamp recordings were conducted on acute rat lumbar spinal cord slices. Considering that both components of Ultiva (remifentanil hydrochloride and glycine) could be involved in NMDA receptor activation, experiments were performed first with remifentanil hydrochloride, second with glycine, and third with the two components within Ultiva. Results Remifentanil hydrochloride does not induce any current, whereas 3 mm glycine induced a current that was abolished by the specific NMDA glutamate site antagonist D-2-amino-5-phosphonovalerate. Ultiva (remifentanil hydrochloride with its vehicle, glycine) also evoked an inward current that was abolished by D-2-amino-5-phosphonovalerate and not significantly different from the glycine-induced current. Application of remifentanil hydrochloride potentiated the NMDA-induced inward current, and this potentiation was abolished by the mu-opioid receptor antagonist naloxone. Conclusion These results show that remifentanil hydrochloride does not directly activate NMDA receptors. The NMDA current recorded after application of Ultiva is related to the presence of glycine. Induced NMDA current is potentiated by application of remifentanil hydrochloride through a pathway involving the mu-opioid receptor.

scholarly journals Distribution and targeting of a mu-opioid receptor (MOR1) in brain and spinal cord

1995 ◽  
Vol 15 (5) ◽  
pp. 3328-3341 ◽  
Author(s):  
U Arvidsson ◽  
M Riedl ◽  
S Chakrabarti ◽  
JH Lee ◽  
AH Nakano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Brain And Spinal Cord

Antinociceptive Effect of Morphine, but not μ Opioid Receptor Number, Is Attenuated in the Spinal Cord of Diabetic Rats

2003 ◽  
Vol 99 (6) ◽  
pp. 1409-1414 ◽  
Author(s):  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Opioid Receptor ◽  
Intrathecal Morphine ◽  
Antinociceptive Effect ◽  
Mu Opioid Receptor ◽  
Diabetic Rats ◽  
Spinal Cord Dorsal Horn ◽  
Mu Opioid ◽  
Spinal Cord Dorsal

Background The mechanisms of decreased analgesic potency of mu opioids in diabetic neuropathic pain are not fully known. The authors recently found that G protein activation stimulated by the mu opioid agonist is significantly reduced in the spinal cord dorsal horn in diabetes. In the current study, they determined potential changes in the number and binding affinity of mu opioid receptors in the spinal cord in diabetic rats. Methods Rats were rendered diabetic with an intraperitoneal injection of streptozotocin. The nociceptive withdrawal threshold was measured before and after intrathecal injection of morphine by applying a noxious pressure stimulus to the hind paw. The mu opioid receptor was determined with immunocytochemistry labeling and a specific mu opioid receptor radioligand, [3H]-(D-Ala2,N-Me-Phe4,Gly-ol5)-enkephalin ([3H]-DAMGO), in the dorsal spinal cord obtained from age-matched normal and diabetic rats 4 weeks after streptozotocin treatment. Results The antinociceptive effect of intrathecal morphine (2-10 microg) was significantly reduced in diabetic rats, with an ED50 about twofold higher than that in normal rats. However, both the dissociation constant (3.99 +/- 0.22 vs. 4.01 +/- 0.23 nm) and the maximal specific binding (352.78 +/- 37.26 vs. 346.88 +/- 35.23 fmol/mg protein) of [3H]-DAMGO spinal membrane bindings were not significantly different between normal and diabetic rats. The mu opioid receptor immunoreactivity in the spinal cord dorsal horn also was similar in normal and diabetic rats. Conclusions The reduced analgesic effect of intrathecal morphine in diabetes is probably due to impairment of mu opioid receptor-G protein coupling rather than reduction in mu opioid receptor number in the spinal cord dorsal horn.

Sign in / Sign up

Export Citation Format

Share Document